Muscle strength, quantity and quality and muscle fat quantity and their association with oxidative stress in patients with facioscapulohumeral muscular dystrophy: Effect of antioxidant supplementation.

The purpose of this study was to identify causes of quadriceps muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). To this aim, we evaluated quadriceps muscle and fat volumes by magnetic resonance imaging and their relationships with muscle strength and oxidative stress markers in adult patients with FSHD (n = 32) and healthy controls (n = 7), and the effect of antioxidant supplementation in 20 of the 32 patients with FSHD (n = 10 supplementation and n = 10 placebo) (NCT01596803). Compared with healthy controls, the dominant quadriceps strength and quality (muscle strength per unit of muscle volume) were decreased in patients with FSHD. In addition, fat volume was increased, without changes in total muscle volume. Moreover, in patients with FSHD, the lower strength of the non-dominant quadriceps was associated with lower muscle quality compared with the dominant muscle. Antioxidant supplementation significantly changed muscle and fat volumes in the non-dominant quadriceps, and muscle quality in the dominant quadriceps. This was associated with improved muscle strength (both quadriceps) and antioxidant response. These findings suggest that quadriceps muscle strength decline may not be simply explained by atrophy and may be influenced also by the muscle intrinsic characteristics. As FSHD is associated with increased oxidative stress, supplementation might reduce oxidative stress and increase antioxidant defenses, promoting changes in muscle function.

Application of bilateral condylectomy as an alternative surgical treatment for Class III malocclusion with posterior vertical excess, a technical note.

The Posterior vertical excess (PVE) associates a symmetric ramus and condyle elongation to an Angle Class III malocclusion. This dento-skeletal discrepancy can be isolated or associated to a condyle hyperplasia or a transverse overgrowth of the mandible due to macroglossia. We present the technique and the postoperative results of bilateral condylectomy applied for the surgical correction of PVE. Bilateral condylectomy represents an alternative to the bimaxillary surgery and adds to the therapeutic arsenal for the correction of Angle Class III malocclusion.

Which sub-compartments of fat mass and fat-free mass are related to blood viscosity factors?

The size of body compartments is a determinant of several factors of blood viscosity. Red cell aggregation is proportional to fat mass while hematocrit is proportional to both fat-free mass and abdominal adiposity, but which parts of these body components are involved in this relationship is not known. Segmental bioelectrical impedance analysis (sBIA) provides a possibility to delineate the relationships more precisely between various subdivisions of the body and blood viscosity factors, going farther than preceding studies using non segmental BIA. In this study we investigated in 38 subjects undergoing a standardized breakfast test with mathematical modelling of glucose homeostasis and a segmental bioelectrical impedance analysis (sBIA) the relationships between the various compartments of the body and viscosity factors. Blood and plasma viscosity were measured with the Anton Paar rheometer and analyzed with Quemada's model. The parameters better correlated to hematocrit are fat free mass (r = 0.562) and its two components muscle mass (r = 0.516) and non-muscular fat-free mass (r = 0.452), and also trunk fat mass (r = 0.383) and waist-to hip ratio (r = 0.394). Red cell aggregation measurements were correlated with both truncal and appendicular fat mass (r ranging between 0.603 and 0.728). Weaker correlations of M and M1 are found with waist circumference and hip circumference. This study shows that the correlation between lean mass and hematocrit involves both muscle and non-muscle moieties of lean mass, and that both central and appendicular fat are determinants of red cell aggregation.

Stability of Le Fort 1 osteotomy in patients with bilateral cleft lip and palate: A retrospective study of 71 patients.

The aim of this study was to evaluate the sagittal and vertical relapses after Le Fort 1 osteotomy in bilateral cleft lip and palate (BCLP) patients. Lateral cephalograms before surgery, immediately after the procedure, at one year, and at least two years (when available) after surgery were superimposed. The positions of five landmarks were studied in a coordinate system. Uni- and multivariate analyses investigated the effect of various factors on the relapse. Of the 71 patients included for a BCLP, 54 presented complete data at one year, and 30 patients were included for the long follow-up study (mean of 55 months). The mean maxillary advancement was 6.2 mm on the sub-spinal point (A). Sagittal relapse occurred at one year (mean of 1.1 mm on point A, 0.7 mm on point prosthion (P); p < 0.0001) and progressed by 0.5 mm and 1.0 mm, respectively, on the same points at the last follow-up. The mean vertical relapse was 0.5 mm on point A (p = 0.044), 0.6 mm on point P (p = 0.16) and 0.5 mm on incisor (I) (p = 0.056). The vertical relapse was correlated to the degree of vertical movement. Three factors were associated to the recurrence including a prior pharyngeal flap, an associated mandibular osteotomy and smoking habits.

Long-term vertical stability of horseshoe osteotomy for the correction of large vertical excess of the maxilla, a retrospective assessment in 15 patients.

INTRODUCTION: Vertical stability after a Le Fort I (LF1) osteotomy with substantial upward movement can be compromised by the position and the volume of the inferior turbinate. A horseshoe (HS) osteotomy represents then an alternative as it preserves the hard palate and the intranasal volume. The aim of this study was to assess the vertical stability of the maxilla after HS osteotomy. MATERIALS AND METHODS: Patients who underwent a HS osteotomy for the correction of long-face syndrome were retrospectively analyzed. The vertical stability was assessed on lateral cephalograms performed preoperatively (T0), immediately postoperatively (T1), and at the last follow-up (T2) by studying points C (the distal cusp of the first maxillary molar), point P (the prosthion, the lowest edge of the maxillary alveolus of the central incisor), and point I (the upper central incisor edge) in a coordinate system. Postoperative complications and aesthetics of the smile were also investigated. RESULTS: Fifteen patients were included (7 females, 8 males, mean age 25.5 ± 9.8 yeras). The mean impaction ranged from 5 mm on point P to 6.1 mm on point C, with a maximal movement of 9.5 mm. A non-significant relapse of 0.8 ± 1.7, 0.6 ± 0.8, and 0.5 ± 1.8 mm was observed after a mean 20.7 months on point C, P, and I respectively. Smile parameters were significantly improved by the procedure, mainly regarding the correction of the gum smile. CONCLUSION: HS osteotomy represents a good alternative to total LF1 osteotomy for substantial maxillary upward movement in long face syndrome deformities.

Nutritional Status of Patients with Facioscapulohumeral Muscular Dystrophy.

In patients with facioscapulohumeral muscular dystrophy (FSHD), a rare genetic neuromuscular disease, reduced physical performance is associated with lower blood levels of vitamin C, zinc, selenium, and increased oxidative stress markers. Supplementation of vitamin C, vitamin E, zinc, and selenium improves the quadriceps' physical performance. Here, we compared the nutritional status of 74 women and 85 men with FSHD. Calorie intake was lower in women with FSHD than in men. Moreover, we assessed vitamin C, vitamin E, zinc, copper, and selenium intakes in diet and their concentrations in the plasma. Vitamin E, copper, and zinc intake were lower in women with FSHD than in men, whereas plasma vitamin C, copper levels, and copper/zinc ratio were higher in women with FSHD than in men. The dietary intake and plasma concentrations of the studied vitamins and minerals were not correlated in both sexes. A well-balanced and varied diet might not be enough in patients with FSHD to correct the observed vitamin/mineral deficiencies. A low energy intake is a risk factor for suboptimal intake of proteins, vitamins, and minerals that are important for protein synthesis and other metabolic pathways and that might contribute to progressive muscle mass loss. Antioxidant supplementation and higher protein intake seem necessary to confer protection against oxidative stress and skeletal muscle mass loss.

Impact of a telerehabilitation programme combined with continuous positive airway pressure on symptoms and cardiometabolic risk factors in obstructive sleep apnea patients.

Background: Obstructive sleep apnea syndrome is a common sleep-breathing disorder associated with adverse health outcomes including excessive daytime sleepiness, impaired quality of life and is well-established as a cardiovascular risk factor. Continuous positive airway pressure is the reference treatment, but its cardiovascular and metabolic benefits are still debated. Combined interventions aiming at improving patient's lifestyle behaviours are recommended in guidelines management of obstructive sleep apnea syndrome but adherence decreases over time and access to rehabilitation programmes is limited. Telerehabilitation is a promising approach to address these issues, but data are scarce on obstructive sleep apnea syndrome. Methods: The aim of this study is to assess the potential benefits of a telerehabilitation programme implemented at continuous positive airway pressure initiation, compared to continuous positive airway pressure alone and usual care, on symptoms and cardiometabolic risk factors of obstructive sleep apnea syndrome. This study is a 6-months multicentre randomized, parallel controlled trial during which 180 obese patients with severe obstructive sleep apnea syndrome will be included. We will use a sequential hierarchical criterion for major endpoints including sleepiness, quality of life, nocturnal systolic blood pressure and inflammation biological parameters. Discussion: m-Rehab obstructive sleep apnea syndrome is the first multicentre randomized controlled trial to examine the effectiveness of a telerehabilitation lifestyle programme in obstructive sleep apnea syndrome. We hypothesize that a telerehabilitation lifestyle intervention associated with continuous positive airway pressure for 6 months will be more efficient than continuous positive airway pressure alone on symptoms, quality of life and cardiometabolic risk profile. Main secondary outcomes include continuous positive airway pressure adherence, usability and satisfaction with the telerehabilitation platform and medico-economic evaluation. Trial registration: Clinicaltrials.gov Identifier: NCT05049928. Registration data: 20 September 2021.

Surgical Repositioning of the Premaxilla: Incidence, Indications and Growth Study About a 189 Bilateral Cleft Lip ± Palate Population.

OBJECTIVE: We aimed to evaluate the rate of patient requiring Surgical Repositioning of the Premaxilla in a population carrying BCL ± P, retrieve age and operative indication. Our secondary objective was to present further facial growth characteristics. SETTINGS: This was a retrospective, single-center cohort study conducted in Nantes University Hospital, Oral and Maxillofacial Surgery department, tertiary cleft center. PATIENTS: Patients with BCL ± P born between 1980 and 2019 treated at Nantes University Hospital were included. MAIN OUTCOME MEASURE: Our primary outcome measure was the rate of patient requiring SRP. RESULTS: Over the whole period, 189 patients with BCL ± P were identified. Three patients (1,58%) underwent SRP. Patients who underwent SRP all had BCLP. SRP was performed during their primary dentition period. The indication for surgical repositioning was always premaxilla vertical overgrowth with an overbite over 10 mm. Facial growth features in the three patients were mostly comparable with a population carrying BCLP who had no premaxillary surgery. CONCLUSION: Our results showed a low incidence of SRP. No SRP was necessary during early infancy (ie, before lip repair) or during adulthood. Surgical repositioning of the premaxilla is beneficial for patient with orthodontically uncorrectable vertical premaxillary excess, even more since facial development compared with other patients with BCLP appears comparable.

Impact of Obstructive Sleep Apnea Syndrome on Ventricular Remodeling after Acute Myocardial Infarction: A Proof-of-Concept Study.

Background: Obstructive sleep apnea syndrome (OSA) is common in patients with acute myocardial infarction (AMI). Whether OSA impacts on the ventricular remodeling post-AMI remains unclear. We compared cardiac ventricular remodeling in patients assessed by cardiac magnetic resonance (CMR) imaging at baseline and six months after AMI based on the presence and severity of OSA. Methods: This prospective study included 47 patients with moderate to severe AMI. They all underwent CMR at inclusion and at six months after an AMI, and a polysomnography was performed three weeks after AMI. Left and right ventricular remodeling parameters were compared between patients based on the AHI, AHI in REM and NREM sleep, oxygen desaturation index, and daytime sleepiness. Results: Of the 47 patients, 49% had moderate or severe OSA with an AHI ≥ 15/h. No differences were observed between these patients and those with an AHI < 15/h for left ventricular end-diastolic and end-systolic volumes at six months. No association was found for left and right ventricular remodeling parameters at six months or for the difference between baseline and six months with polysomnographic parameters of OSA severity, nor with daytime sleepiness. Conclusions: Although with a limited sample size, our proof-of-concept study does not report an association between OSA and ventricular remodeling in patients with AMI. These results highlight the complexity of the relationships between OSA and post-AMI morbi-mortality.

ANT1 overexpression models: Some similarities with facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by progressive muscle weakness. Adenine nucleotide translocator 1 (ANT1), the only 4q35 gene involved in mitochondrial function, is strongly expressed in FSHD skeletal muscle biopsies. However, its role in FSHD is unclear. In this study, we evaluated ANT1 overexpression effects in primary myoblasts from healthy controls and during Xenopus laevis organogenesis. We also compared ANT1 overexpression effects with the phenotype of FSHD muscle cells and biopsies. Here, we report that the ANT1 overexpression-induced phenotype presents some similarities with FSHD muscle cells and biopsies. ANT1-overexpressing muscle cells showed disorganized morphology, altered cytoskeletal arrangement, enhanced mitochondrial respiration/glycolysis, ROS production, oxidative stress, mitochondrial fragmentation and ultrastructure alteration, as observed in FSHD muscle cells. ANT1 overexpression in Xenopus laevis embryos affected skeletal muscle development, impaired skeletal muscle, altered mitochondrial ultrastructure and led to oxidative stress as observed in FSHD muscle biopsies. Moreover, ANT1 overexpression in X. laevis embryos affected heart structure and mitochondrial ultrastructure leading to cardiac arrhythmia, as described in some patients with FSHD. Overall our data suggest that ANT1 could contribute to mitochondria dysfunction and oxidative stress in FSHD muscle cells by modifying their bioenergetic profile associated with ROS production. Such interplay between energy metabolism and ROS production in FSHD will be of significant interest for future prospects.

Impact of Orthodontic Gap Closure versus Prosthetic Replacement of Missing Maxillary Lateral Incisor on Dental Arch Relationships and Symmetry in 212 Patients with Cleft Palate: Retrospective Study.

BACKGROUND: Maxillary lateral incisors are frequently missing in patients with cleft lip and/or palate. The aim of this study was to assess how orthodontic gap closure or prosthetic rehabilitation of the missing maxillary lateral incisor affected dental arch relationships and symmetry at the end of treatment. The authors also aimed to determine the effect of the level of oral hygiene on the decision made to manage the missing maxillary lateral incisor gap. METHODS: A descriptive, retrospective cohort study including all patients with cleft lip and/or palate born between 1980 and 1999 and treated at Nantes Cleft Center was performed. Patients presenting unilateral or bilateral missing maxillary lateral incisors were reviewed. Data on management of the missing incisor gap, dental arch relationships, symmetry, and level of oral hygiene were collected. RESULTS: A total of 486 patients with cleft lip and/or palate were reviewed, including 212 patients with unilateral or bilateral missing maxillary lateral incisors. When compared with orthodontic gap closure, prosthetic replacement of the gap was associated with better final dental arch relationships (59.8 percent versus 10.3 percent; p < 0.01) and better dental arch symmetry (88.1 percent versus 44.0 percent; p < 0.01) for patients with unilateral missing incisors but not for patients with bilateral missing incisors. A higher level of oral hygiene was associated with more cases of prosthetic replacement for patients with unilateral missing incisors ( p = 0.03) but had no effect for patients with bilateral missing incisors. CONCLUSION: Prosthetic replacement of the missing maxillary lateral incisor gap provided better functional and aesthetic results for patients with cleft lip and/or palate presenting with unilateral missing maxillary lateral incisor.

Biomarkers of Redox Balance Adjusted to Exercise Intensity as a Useful Tool to Identify Patients at Risk of Muscle Disease through Exercise Test.

The screening of skeletal muscle diseases constitutes an unresolved challenge. Currently, exercise tests or plasmatic tests alone have shown limited performance in the screening of subjects with an increased risk of muscle oxidative metabolism impairment. Intensity-adjusted energy substrate levels of lactate (La), pyruvate (Pyr), ß-hydroxybutyrate (BOH) and acetoacetate (AA) during a cardiopulmonary exercise test (CPET) could constitute alternative valid biomarkers to select "at-risk" patients, requiring the gold-standard diagnosis procedure through muscle biopsy. Thus, we aimed to test: (1) the validity of the V'O2-adjusted La, Pyr, BOH and AA during a CPET for the assessment of the muscle oxidative metabolism (exercise and mitochondrial respiration parameters); and (2) the discriminative value of the V'O2-adjusted energy and redox markers, as well as five other V'O2-adjusted TCA cycle-related metabolites, between healthy subjects, subjects with muscle complaints and muscle disease patients. Two hundred and thirty subjects with muscle complaints without diagnosis, nine patients with a diagnosed muscle disease and ten healthy subjects performed a CPET with blood assessments at rest, at the estimated 1st ventilatory threshold and at the maximal intensity. Twelve subjects with muscle complaints presenting a severe alteration of their profile underwent a muscle biopsy. The V'O2-adjusted plasma levels of La, Pyr, BOH and AA, and their respective ratios showed significant correlations with functional and muscle fiber mitochondrial respiration parameters. Differences in exercise V'O2-adjusted La/Pyr, BOH, AA and BOH/AA were observed between healthy subjects, subjects with muscle complaints without diagnosis and muscle disease patients. The energy substrate and redox blood profile of complaining subjects with severe exercise intolerance matched the blood profile of muscle disease patients. Adding five tricarboxylic acid cycle intermediates did not improve the discriminative value of the intensity-adjusted energy and redox markers. The V'O2-adjusted La, Pyr, BOH, AA and their respective ratios constitute valid muscle biomarkers that reveal similar blunted adaptations in muscle disease patients and in subjects with muscle complaints and severe exercise intolerance. A targeted metabolomic approach to improve the screening of "at-risk" patients is discussed.

Beyond the Calorie Paradigm: Taking into Account in Practice the Balance of Fat and Carbohydrate Oxidation during Exercise?

Recent literature shows that exercise is not simply a way to generate a calorie deficit as an add-on to restrictive diets but exerts powerful additional biological effects via its impact on mitochondrial function, the release of chemical messengers induced by muscular activity, and its ability to reverse epigenetic alterations. This review aims to summarize the current literature dealing with the hypothesis that some of these effects of exercise unexplained by an energy deficit are related to the balance of substrates used as fuel by the exercising muscle. This balance of substrates can be measured with reliable techniques, which provide information about metabolic disturbances associated with sedentarity and obesity, as well as adaptations of fuel metabolism in trained individuals. The exercise intensity that elicits maximal oxidation of lipids, termed LIPOXmax, FATOXmax, or FATmax, provides a marker of the mitochondrial ability to oxidize fatty acids and predicts how much fat will be oxidized over 45-60 min of low- to moderate-intensity training performed at the corresponding intensity. LIPOXmax is a reproducible parameter that can be modified by many physiological and lifestyle influences (exercise, diet, gender, age, hormones such as catecholamines, and the growth hormone-Insulin-like growth factor I axis). Individuals told to select an exercise intensity to maintain for 45 min or more spontaneously select a level close to this intensity. There is increasing evidence that training targeted at this level is efficient for reducing fat mass, sparing muscle mass, increasing the ability to oxidize lipids during exercise, lowering blood pressure and low-grade inflammation, improving insulin secretion and insulin sensitivity, reducing blood glucose and HbA1c in type 2 diabetes, and decreasing the circulating cholesterol level. Training protocols based on this concept are easy to implement and accept in very sedentary patients and have shown an unexpected efficacy over the long term. They also represent a useful add-on to bariatric surgery in order to maintain and improve its weight-lowering effect. Additional studies are required to confirm and more precisely analyze the determinants of LIPOXmax and the long-term effects of training at this level on body composition, metabolism, and health.

Outcomes of functional treatment of condylar mandibular fractures with an articular impact: a retrospective study of 108 children.

INTRODUCTION: The treatment of fractures of the mandibular condylar process remains controversial, especially in children. The aim of this study was to assess the long-term clinical and radiographic outcomes of functional treatments for mandibular condylar fractures with an articular impact. MATERIALS AND METHODS: Young patients (< 15 years of age) presenting with either a unilateral or a bilateral mandibular fracture of the condylar process were included in this retrospective study. The clinical analysis focused on investigation of joint amplitudes at 1, 2, 6, 12, and 24 months after the beginning of the treatment, and at the end of their physical growth for the long-term study. Other clinical parameters included temporomandibular joint (TMJ) disorders and facial asymmetry. Photographs of patients and panoramic X-rays were assessed to identify any growth disorders at the end of the follow-up. RESULTS: One hundred and eight patients were included in this study, and 33 patients who were no longer undergoing mandibular growth at the time of the last follow-up were included in the long-term study. The mean age at the time of the trauma was 9.33 years, and the mean follow-up was 82.2 months. A significant improvement was observed in the maximal mouth opening (MMO), diduction, and propulsion in the first months after the trauma, reaching 44.31 mm (p < 0.0001), 10.50 mm (p = 0.0001), and 6.33 mm (p = 0.01), respectively, at 6 months. Three patients experienced a clinical posterior vertical insufficiency, one of which required a surgical procedure, while four patients exhibited a ramus asymmetry of up to 10 mm, albeit with no clinical consequences. One case of TMJ ankylosis was noted. CONCLUSION: Our study suggests that functional treatment is appropriate for fractures of the mandibular condyle with an articular impact in children, as it promotes mandibular growth and good functional recovery. Children have to be followed up, however, until completion of growth.

Impact of a Mobile Telerehabilitation Solution on Metabolic Health Outcomes and Rehabilitation Adherence in Patients With Obesity: Randomized Controlled Trial.

BACKGROUND: Obesity is a major public health issue. Combining exercise training, nutrition, and therapeutic education in metabolic rehabilitation (MR) is recommended for obesity management. However, evidence from randomized controlled studies is lacking. In addition, MR is associated with poor patient adherence. Mobile health devices improve access to MR components. OBJECTIVE: The aim of this study is to compare the changes in body composition, anthropometric parameters, exercise capacity, and quality of life (QOL) within 12 weeks of patients in the telerehabilitation (TR) program to those of usual care patients with obesity. METHODS: This was a parallel-design randomized controlled study. In total, 50 patients with obesity (BMI>30 kg/m²) were included in a TR group (TRG) or a usual care group (UCG) for 12 weeks. Patients underwent biometric impedance analyses, metabolic exercise tests, actimetry, and QOL and satisfaction questionnaires. The primary outcome was the change in fat mass at 12 weeks from baseline. Secondary outcomes were changes in body weight, metabolic parameters, exercise capacity, QOL, patients' adhesion, and satisfaction. RESULTS: A total of 49 patients completed the study. No significant group × time interaction was found for fat mass (TRG: mean 1.7 kg, SD 2.6 kg; UCG: mean 1.2 kg, SD 2.4 kg; P=.48). Compared with the UCG, TRG patients tended to significantly improve their waist to hip ratios (TRG: -0.01 kg, SD 0.04; UCG: +0.01 kg, SD 0.06; P=.07) and improved QOL physical impact (TRG: +21.8, SD 43.6; UCG: -1.2, SD 15.4; P=.005). Significant time effects were observed for body composition, 6-minute walk test distance, exercise metabolism, sedentary time, and QOL. Adherence (95%) and satisfaction in the TRG were good. CONCLUSIONS: In adults with obesity, the TR program was not superior to usual care for improving body composition. However, TR was able to deliver full multidisciplinary rehabilitation to patients with obesity and improve some health outcomes. Given the patients' adherence and satisfaction, pragmatic programs should consider mobile health devices to improve access to MR. Further studies are warranted to further establish the benefits that TR has over usual care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03396666; http://clinicaltrials.gov/ct2/show/NCT03396666.

Prognostic Impact of Sleep Patterns and Related-Drugs in Patients with Heart Failure.

Sleep disturbances are frequent among patients with heart failure (HF). We hypothesized that self-reported sleep disturbances are associated with a poor prognosis in patients with HF. A longitudinal study of 119 patients with HF was carried out to assess the association between sleep disturbances and the occurrence of major cardiovascular events (MACE). All patients with HF completed self-administered questionnaires on sleepiness, fatigue, insomnia, quality of sleep, sleep patterns, anxiety and depressive symptoms, and central nervous system (CNS) drugs intake. Patients were followed for a median of 888 days. Cox models were used to estimate the risk of MACE associated with baseline sleep characteristics. After adjustment for age, the risk of a future MACE increased with CNS drugs intake, sleep quality and insomnia scores as well with increased sleep latency, decreased sleep efficiency and total sleep time. However, after adjustment for left ventricular ejection fraction and hypercholesterolemia the HR failed to be significant except for CNS drugs and total sleep time. CNS drugs intake and decreased total sleep time were independently associated with an increased risk of MACE in patients with HF. Routine assessment of self-reported sleep disturbances should be considered to prevent the natural progression of HF.

Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Age and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis. To overcome these confounding factors, alterations in skeletal muscle were analyzed in highly selected patients on long-term hemodialysis undergoing kidney transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 22 patients on long-term hemodialysis scheduled for kidney transplantation with few comorbidities, but with a long-term uremic milieu exposure, and 22 age, sex, and physical activity level frequency-matched control participants were recruited. We compared biochemical, functional, and molecular characteristics of the skeletal muscle using maximal voluntary force and endurance of the quadriceps, 6-minute walking test, and muscle biopsy of vastus lateralis. For statistical analysis, mean comparison and multiple regression tests were used. RESULTS: In patients on long-term hemodialysis, muscle endurance was lower, whereas maximal voluntary force was not significantly different. We observed a transition from type I (oxidative) to type II (glycolytic) muscle fibers, and an alteration of mitochondrial structure (swelling) without changes in DNA content, genome replication (peroxisome proliferator activator receptor γ coactivator-1α and mitochondrial transcription factor A), regulation of fusion (mitofusin and optic atrophy 1), or fission (dynamin-related protein 1). Notably, there were autophagosome structures containing glycogen along with mitochondrial debris, with a higher expression of light chain 3 (LC3) protein, indicating phagophore formation. This was associated with a greater conversion of LC3-I to LC3-II and the expression of Gabaralp1 and Bnip3l genes involved in mitophagy. CONCLUSIONS: In this highly selected long-term hemodialysis population, a low oxidative phenotype could be defined by a poor endurance, a fiber-type switch, and an alteration of mitochondria structure, without evidence of sarcopenia. This phenotype could be related to uremia through the activation of autophagy/mitophagy. CLINICAL TRIAL REGISTRATION NUMBERS: NCT02794142 and NCT02040363.

Dynapaenia and sarcopaenia in chronic haemodialysis patients: do muscle weakness and atrophy similarly influence poor outcome?

BACKGROUND: Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients. METHODS: Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median). RESULTS: From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7-82.0) years], 44 died during the follow-up period of 23.7 (12.4-34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18-7.61; P = 0.02]. CONCLUSIONS: Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage.